The overall aim is to increase our understanding of the mechanism of gene regulation in higher cells. To this end a dual approach will be used. Studies of RNA synthesis by labeling methods and the diversity of transcripts produced in various mammalian cells by DNA/RNA hybridization reflect the primary activity of the genome. Secondly, the structure of the eukaryotic chromosome is investigated through attempts to fractionate chromatin into active and inactive regions. This has been accomplished by several means and it now remains to analyze the physical and chemical attributes of these chromatin fractions in order to understand the basis of selective gene expression and its relationship to chromosome structure. A major attack on this problem will involve studies of histones and non-histone chromosomal proteins and their metabolism.